A reassessment of the neurotoxicity of pyrethroid insecticides

The pyrethroids are a widely used class of insecticides to which there is significant human exposure. They are however generally regarded as safe to man, and there have been few reports of human fatalities. Their acute toxicity is dominated by pharmacological actions upon the central nervous system (CNS), predominantly mediated by prolongation of the kinetics of voltage-gated sodium channels, although other mechanisms operate. This review summarizes our present understanding of such actions and the pharmacological options to antagonize them. One significant problem is the very clear heterogeneity of pyrethroid sensitivity that is seen across sodium channel subtypes; however, the distribution and function of these across the central nervous system are poorly characterized. The review also provides an overview of recent studies that suggest additional effects of pyrethroids: developmental neurotoxicity, the production of neuronal death, and action mediated via pyrethroid metabolites. The evidence for these is at present equivocal, but all 3 carry important implications for human health.